Naslov
Listeria monocytogenes (delta-actA mutant) infection in tumor necrosis factor receptor p55-deficient neonatal mice

Autori
Bubonja Sonje, Marina ; Abram, Maja ; Stenzel, Werner ; Deckert, Martina

Izvornik
Microbial pathogenesis (0882-4010) 49 (2010), 4; 186-195

Vrsta, podvrsta i kategorija rada
Radovi u časopisima, članak, znanstveni

Ključne riječi
Listeria monocytogenes; TNFR1; newborn mice; chemokines; cytokines; IDO; iNOS

Sažetak
Using TNF receptor 1 knock out (TNFR1KO) mice, we investigated the role played by TNFR1 in immune regulation during neonatal listeriosis. Induction of protective immune response in wild type pups resulted in the prompt control of infection with an attenuated ∆actA mutant L. monocytogenes, accompanied by enhanced hepatic expression of mRNA for IFN-gamma, TNF-alpha, and IL-10. Conversely, the lack of TNFR1 signalling in TNFR1KO neonatal mice resulted in substantial changes in the profile of inflammatory mediators and ultimately fatal outcome of the infected pups, which experienced increasingly severe hepatitis, meningitis, and brain abscesses. Despite remarkable increase in indoleamine 2, 3-dioxygenase (IDO) and inducible nitric oxide synthase (iNOS) mRNA detected in the liver of TNFR1KO mice, bacterial proliferation was unrestrained. Increased mRNA expression of IDO, iNOS, TNF-alpha, IFN-gamma, MCP-1, and MIP-1alpha was found in the spleens of infected KO mice, and in the brains mRNA encoding iNOS, IDO, IFN-gamma, IL-12p40, IL-10, and RANTES was also upregulated. In addition to the exaggerated production of inflammatory mediators, large necrotic lesions consisting of granulocytes and macrophages were scattered throughout the liver of these mice. TNFR1KO neonates were unable to clear neutrophils and switch from the innate immune response to a specific reaction mediated by T-cells. The loosely associated lymphocyte and macrophage infiltrates in the liver of TNFR1KO mice failed to form granulomas and to prevent progressive infection. These results prove that TNF-alpha signalling through TNFR1 mediating mRNA expression of different inflammatory mediators is crucial and irreplaceable in antilisterial protection during the neonatal period.

Izvorni jezik
Engleski

Znanstvena područja
Temeljne medicinske znanosti, Kliničke medicinske znanosti

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